Seminars in Fetal and Neonatal Medicine (Semin Fetal Neonatal Med)

Publications in this journal

• Article: Offspring of diabetic pregnancy: short-term outcomes.

  A Michael Weindling
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  ABSTRACT: In spite of clinicians apparently appreciating the risks of maternal diabetes to the baby, babies of mothers with diabetes are still at increased risk compared to those of non-diabetic women. The rate of prematurity in infants of diabetic mothers is five times that of the general population. Women with pre-gestational diabetes give birth to larger babies. In a recent study, half were above the 90th centile for weight. The postnatal management of these babies continues to give cause for concern. In a recent UK study, over half of all infants of diabetic mothers were admitted to a neonatal unit. One-third of these were at term. This admission rate is three times the UK average and examination of cases showed that two-thirds of admissions were unnecessary. It is likely that a high maternal blood glucose concentration is the most important factor causing this increased risk. Babies of women with type 1 and type 2 DM have similar complication rates. Tighter preconceptional glycaemic control as well as during the pregnancy is likely to be important in improving outcome for the babies of diabetic mothers.
  Seminars in Fetal and Neonatal Medicine 05/2009; 14(2):111-8.
• Article: Perinatal programming and reprogramming by glucocorticoid therapy and perinatal stress.

  Frank van Bel, Cobi J Heijnen
  Seminars in Fetal and Neonatal Medicine 03/2009; 14(3):127-9.
• Article: Epigenetic effects of glucocorticoids.

  Ian C G Weaver
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  ABSTRACT: The early nurturing environment has persistent influences on developmental programming of inter-individual differences in metabolic and endocrine function that contribute to emotional and cognitive performance through life. These effects are mediated, in part, through neonatal programming of hypothalamic-pituitary-adrenal (HPA) axis function. Animal models support this hypothesis. For example, in the rat natural variations in maternal care influence HPA axis stress reactivity in the offspring via long-term changes in tissue-specific gene expression. Studies in vivo and in vitro show that maternal licking and grooming increases glucocorticoid receptor expression in the offspring via increased hippocampal serotonergic tone accompanied by increased histone acetylase transferase activity, histone acetylation and DNA demethylation mediated by the transcription factor nerve growth factor-inducible protein-A. These effects are reversed by early postnatal cross-fostering and by pharmacological manipulations, including trichostatin A (TSA) and l-methionine administration in adulthood. These studies demonstrate that an epigenetic state of a gene can be established through early in life experience, and is potentially reversible in adult life. Accordingly, epigenetic modifications in target gene promoters in response to environmental demand may ensure stable yet dynamic regulation that mediates persistent changes in biological and behavioral phenotype over the lifespan.
  Seminars in Fetal and Neonatal Medicine 03/2009; 14(3):143-50.
• Article: Neonatal glucose metabolism in offspring of mothers with varying degrees of hyperglycemia during pregnancy.

  Bengt Persson
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  ABSTRACT: The definition of neonatal hypoglycemia is controversial. Operational thresholds of blood glucose values at which intervention should be considered have been proposed. IDM and GDM infants frequently exhibit a pronounced drop of plasma glucose immediately after birth. This exaggerated physiological decline of glucose is transient and is seldom accompanied by suppressed lipolysis or clinical symptoms. It is generally attributed to hyperinsulinism elicited by maternal hyperglycemia. Alternative substrates for CNS i.e. lactate and astrocyte glycogen may explain lack of symptoms. Similarly low glucose values later on may cause clinical symptoms. Glucose production rates vary from attenuated to normal likely reflecting differences in maternal glycemic control. The HAPO study of around 25,000 non-diabetic pregnancies revealed strong associations between glucose values (75g OGTT) and increased fetal size and hyperinsulinemia at birth - findings adding strong support to the maternal hyperglycemia - fetal hypinsulinism theory. Mothers with the highest fasting glucose had infants with the highest frequency of clinical neonatal hypoglycaemia (4,6%).
  Seminars in Fetal and Neonatal Medicine 03/2009; 14(2):106-10.
• Article: Offspring of diabetic pregnancy: long-term outcomes.

  Umberto Simeoni, David J Barker
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  ABSTRACT: Diabetes in pregnancy has been shown to induce long-term effects in offspring. While considerable attention is focused on the increased incidence of type 2 diabetes mellitus (T2DM) in adult offspring from diabetic mothers, cardiovascular alterations, including hypertension, are also part of lifelong consequences of in-utero exposure to increased glucose concentrations. This review examines the epidemiologic and mechanistic issues involved in the developmental programming of long-term consequences in offspring of diabetic mothers, with a particular emphasis on the renal and vascular mechanisms of hypertension. The factors of increased incidence of T2DM and of obesity in adults born after exposure to diabetes during pregnancy are also discussed, as evidence is accumulating that a vicious circle involving lifelong consequences of diabetes in pregnancy in offspring contributes to the current worldwide epidemic of T2DM.
  Seminars in Fetal and Neonatal Medicine 03/2009; 14(2):119-24.
• Article: Establishing diagnosis of gestational diabetes mellitus: Impact of the hyperglycemia and adverse pregnancy outcome study.

  Yariv Yogev, Boyd E Metzger, Moshe Hod
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  ABSTRACT: The diagnosis of gestational diabetes mellitus (GDM) remains controversial, without universal acceptance of a particular set of diagnostic criteria, and, in fact, a lack of consensus as to whether this is an entity worth diagnosis. Some of the debate derives from differences of opinion about what degree of glucose intolerance should be labeled as GDM. Therefore, it is to be expected that there are different viewpoints on how to detect and screen for GDM. It is believed that early diagnosis will result in a significant improvement in perinatal outcome in these patients. In this review, we discuss the current data concerning screening for GDM and new strategies for GDM diagnosis in light of the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) study.
  Seminars in Fetal and Neonatal Medicine 03/2009; 14(2):94-100.
• Article: Congenital anomalies in diabetic pregnancy.

  Ulf J Eriksson
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  ABSTRACT: Congenital malformations are more common in infants of diabetic women than in children of non-diabetic women. The etiology, pathogenesis and prevention of the diabetes-induced malformations have spurred considerable clinical and basic research efforts. The ultimate aim of these studies has been to obtain an understanding of the teratogenic process, which may enable precise preventive therapeutic measures in diabetic pregnancies. The results of the clinical and basic studies support the view of an early gestational induction of the malformations in diabetic pregnancy by a teratogenic process of multifactorial etiology. There may be possible targets for new therapeutic efforts revealed by the research work. Thus, future additions to the therapeutic efforts may include supplementation with antioxidants and/or folic acid, although more research is needed to delineate the dosages and compounds to be used. As the research into genetic predisposition for the teratogenic induction of malformations by maternal diabetes starts to reveal new genes and gene products involved in the etiology of the malformations, a set of new targets for intervention may arise.
  Seminars in Fetal and Neonatal Medicine 02/2009; 14(2):85-93.
• Article: The fetus of a diabetic mother: sonographic evaluation.

  Jacky Nizard, Yves Ville
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  ABSTRACT: Maternal hyperglycemia is responsible for many fetal adverse outcomes. Ultrasound examination of these pregnancies aims at an early detection of congenital malformations, assessment of fetal well-being, and fetal growth. This evaluation will influence clinical decision in determining the best time and mode of delivery. We reviewed data from the literature on accuracy, usefulness, and indications of ultrasound examinations in pregnancies complicated with diabetes mellitus, whether pregestational or gestational.
  Seminars in Fetal and Neonatal Medicine 02/2009; 14(2):101-5.
• Article: Should we be prescribing repeated courses of antenatal corticosteroids?

  John P Newnham, Alan H Jobe
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  ABSTRACT: Single-course treatment with antenatal corticosteroids has been shown to enhance fetal maturation before preterm birth and to improve outcomes for the preterm infant. Based on this success, practitioners expanded use of the treatment to repeated courses of antenatal corticosteroids ahead of evidence demonstrating benefit and excluding harm. Experiments with animals and cohort studies have provided a body of evidence suggesting that repeated doses may further improve lung maturation but may be accompanied by deleterious effects on the developing brain and other organs. Randomised controlled trials of repeated treatments to date have provided mixed evidence but in general may indicate a small benefit in terms of postnatal lung function, but this is accompanied by restricted growth which may include the brain. In view of the well-established role that corticosteroids are known to play in brain development, and the marginal difference that repeated courses may make to outcome in the context of modern neonatal care, antenatal corticosteroid treatments should be restricted to single-course treatment.
  Seminars in Fetal and Neonatal Medicine 01/2009; 14(3):157-63.
• Article: Fundamental aspects of the impact of glucocorticoids on the (immature) brain.

  Danielle L Champagne, E Ronald de Kloet, Marian Joëls
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  ABSTRACT: In this review, studies on the role of glucocorticoids during brain development are recapitulated with reference to their immediate effects and long-term impact on central functions. Traditionally, this research has focused on detrimental consequences of stress and exogenous glucocorticoid exposure but far less on the ability to develop resilience to stress despite exposure to early adversity. Recent findings suggest that the impact of early life conditions turns out as either harmful or protective depending on later environmental context. To explain this, the concept of 'predictive adaptive response' was introduced, implying that early-life conditions may prepare for life ahead through glucocorticoid programming and phenotypic plasticity with the goal to 'match' future environmental demands. This concept has led to the hypothesis that a 'mismatch' between early and later life conditions can enhance vulnerability to disease.
  Seminars in Fetal and Neonatal Medicine 01/2009; 14(3):136-42.
• Article: Antenatal corticosteroid therapy: short-term effects on fetal behaviour and haemodynamics.

  E J H Mulder, R de Heus, G H A Visser
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  ABSTRACT: Antenatal corticosteroid therapy to enhance fetal lung maturity in threatened preterm delivery has a number of non-pulmonary side-effects, both beneficial and undesirable. This review focuses on the short-term (transient) effects of betamethasone and dexamethasone on aspects of fetal circulation and behaviour which are used clinically as markers of fetal well-being. We summarise the effects observed, discuss the proposed underlying mechanisms, and emphasise the consequences for clinical decision-making. Recommendations are given to optimise medical care and to minimise the risk of unwarranted iatrogenic preterm delivery.
  Seminars in Fetal and Neonatal Medicine 01/2009; 14(3):151-6.
• Article: Impact of perinatal corticosteroids on neuromotor development and outcome: review of the literature and new meta-analysis.

  E S Shinwell, S Eventov-Friedman
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  ABSTRACT: Perinatal corticosteroids are like a double-edged sword. On the one hand, they reduce risk for major morbidity and even mortality; on the other hand, they modify growth and development of body systems, with short- and long-term consequences. The relationship between corticosteroids and neurodevelopmental outcome has been extensively studied in randomized controlled trials, cohort and case-control studies and meta-analyses. In this article we attempt accurately to reflect current clinical equipoise on this issue by reviewing the most recent literature and adding a new meta-analysis on the relationship between postnatal dexamethasone and cerebral palsy and neurodevelopmental impairment.
  Seminars in Fetal and Neonatal Medicine 01/2009; 14(3):164-70.
• Article: Long-term effects of neonatal hydrocortisone treatment for chronic lung disease on the developing brain and heart.

  Karin J Rademaker, Willem B de Vries
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  ABSTRACT: Despite modern perinatal intensive care techniques, chronic lung disease remains a problem in preterm-born infants. The most commonly and almost exclusively prescribed drug to treat this disorder is dexamethasone. Corticosteroids improve short-term respiratory function; however, many side-effects have been reported and the adverse long-term effects of dexamethasone on neurodevelopment are particularly alarming. Hydrocortisone could be a suitable alternative for dexamethasone, if equally effective with fewer side-effects. This review evaluates the current literature on neonatal hydrocortisone treatment for chronic lung disease with regards to long-term neurodevelopmental outcome and cardiovascular effects. The neurodevelopmental studies do not show any adverse effects of hydrocortisone on neurocognitive and motor outcome, nor on incidence of brain abnormalities on magnetic resonance imaging or on long-lasting programming effects on the hypothalamus-pituitary-adrenal axis. At school age, cardiovascular stress response was the same in hydrocortisone-treated children compared with a reference group. Hydrocortisone seems a safe alternative to dexamethasone, but more double-blind randomised studies are needed.
  Seminars in Fetal and Neonatal Medicine 01/2009; 14(3):171-7.
• Article: Glucocorticoids and neuro- and behavioural development.

  Ana Raquel Mesquita, Yvonne Wegerich, Alexandre V Patchev, Mario Oliveira, Pedro Leão, Nuno Sousa, Osborne F X Almeida
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  ABSTRACT: Epidemiological evidence links exposure to stress hormones during fetal or early postnatal development with lifetime prevalence of cardiac, metabolic, auto-immune, neurological and psychiatric disorders. This has led to the concept of 'developmental programming through stress'. Importantly, these effects (specifically, hypertension, hyperglycaemia and neurodevelopmental and behavioural abnormalities) can be reproduced by exposure to high glucocorticoid levels, indicating a crucial role of glucocorticoids in their causation. However, there can be important differences in outcome, depending on the exact time of exposure, as well as duration and receptor selectivity of the glucocorticoid applied. The mechanisms underlying programming by stress are still unclear but it appears that these environmental perturbations exploit epigenetic modifications of DNA and/or histones to induce stable modifications of gene expression. Programming of neuro- and behavioural development by glucocorticoids and stress are important determinants of lifetime health and should be a consideration when choosing treatments in obstetric and neonatal medicine.
  Seminars in Fetal and Neonatal Medicine 01/2009; 14(3):130-5.
• Article: New modalities in the treatment of pregnancies complicated by diabetes: drugs and devices.

  Lironn Chitayat, Lois Jovanovic, Moshe Hod
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  ABSTRACT: The development of drugs and devices in the treatment of pregnancies complicated by diabetes is in constant forward progression to compensate for pancreatic beta cell insufficiency. Maternal hyperglycemia during pregnancy is of particular interest due to the severe consequences that surface when a fetus is in development. The drugs that are currently recommended for use during pregnancy include rapid-acting insulin analogs lispro and aspart for meal-related bolus insulin and intermediate-acting NPH for basal insulin. Oral anti-diabetic agents are not recommended for use during pregnancy. Better control may be achieved with the incorporation of real-time glucose sensors and new insulin pumps with hopes of improving pregnancy outcome.
  Seminars in Fetal and Neonatal Medicine 01/2009; 14(2):72-6.
• Article: The simulated delivery-room environment as the future modality for acquiring and maintaining skills in fetal and neonatal resuscitation.

  Louis P Halamek
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  ABSTRACT: The science underlying neonatal resuscitation is growing exponentially in quantity and quality. So, too, is the knowledge of effective methodologies that facilitate acquisition and maintenance of the cognitive, technical, and behavioral skills necessary to for successful resuscitation of the newborn. One of these methodologies, simulation-based training, offers many advantages over more traditional methodologies: By providing key visual, auditory, and tactile cues it creates a high level of physical, biological, and psychological fidelity to the real environment and thus is able to elicit realistic responses from trainees. Training scenarios coupled with debriefings (where discussion of what went well and what could be improved upon occur in a nonjudgmental fashion) provide rich learning experiences that rival or exceed those in the real clinical environment. Simulation-based training will likely become the standard for not only routine training but also high-stakes assessment such as licensure and board certification.
  Seminars in Fetal and Neonatal Medicine 12/2008; 13(6):448-53.
• Article: Maternal, fetal and neonatal complications of diabetic pregnancy-delivering optimal care while awaiting for cure.

  Moshe Hod, Umberto Simeoni
  Seminars in Fetal and Neonatal Medicine 12/2008; 14(2):63-5.
• Article: Normal and abnormal maternal metabolism during pregnancy.

  David R Hadden, Ciara McLaughlin
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  ABSTRACT: Metabolic adaptations during pregnancy are essential to meet the physiological demands of pregnancy as well as adequate growth and development of the fetus. There has been considerable interest in carbohydrate metabolism during pregnancy, with diabetes, the main disorder of glucose metabolism, a considerable focus for research. Whereas disorders of protein and lipid metabolism are recognised during pregnancy, their influence has received less attention. Fasting glucose values fall in early pregnancy with a rise in plasma free fatty acids, enhanced ketogenesis and a fall in plasma amino acids. Decreased hepatic insulin sensitivity in later pregnancy plays a key role in bringing about the appropriate changes in carbohydrate, lipid and amino acid metabolism which are essential for normal fetal development and survival.
  Seminars in Fetal and Neonatal Medicine 12/2008; 14(2):66-71.